Phospholipase D2 in prostate cancer: protein expression changes with Gleason score

Noble, Amanda; Hogg, Karen; Suman, Rakesh; Berney, Daniel M.; Bourgoin, Sylvain G.; Maitland, Norman J.; Rumsby, Martin G.

doi:10.1038/s41416-019-0610-7

Cited by 5 publications

(11 citation statements)

References 111 publications

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“…The unique and scarce patient-derived primary PCa cells used here, as in our earlier work 9,24 , have a basal cell phenotype (CK5 + / CK8 -/ AR -/ CD49b + / CD44 + / CD24 + ) 45,46 . These are the main cells cultured from PCa biopsy tissue because tumorigenic luminal cells which account for the bulk of PCa tissue do not adapt to culture as they are terminally differentiated.…”

Section: Discussionmentioning

confidence: 83%

“…The PC3 prostate epithelial cell line was cultured as described in Noble et al 9,24 . Primary PCa epithelial cells were purified from human prostate tissue samples which were obtained with patient consent and full ethical approval (South Yorkshire Research Ethics Committee, Yorkshire and the Humber, REC:07/H1304/121) as previously stated 24 .…”

Section: Cell Isolation and Culturementioning

confidence: 99%

“…The copyright holder for this preprint this version posted May 20, 2021. ; https://doi.org/10.1101/2021.05.19.444795 doi: bioRxiv preprint 5.7M, JWJ 3.2M), these concentrations being based on results from our previous inhibition studies. 9,24 After 48 hours 5-ethynyl-2'-deoxyuridine (EdU) was added and after a further 24 hours the cells were harvested according to the manufacturer's protocol. Results were acquired on a CyAn ADP flow cytometer using Summit software.…”

Section: Pld Inhibition and The Cell Cyclementioning

confidence: 99%

“…Both PLD1 and PLD2 are implicated in tumorigenesis since total PLD activity and PLD1/PLD2 protein expression are elevated in many cancers and often correlate with prognosis [1][2][3][4][5][6][7][8] . In prostate cancer (PCa) we have reported that PLD2 protein expression correlates with increasing Gleason score (GS) from GS6 to GS8 but is decreased in GS9 tissue where gland structure is not evident 9 . Stable fibroblast cell lines over-expressing PLD1 or PLD2 show increased proliferation, enhanced colony formation in soft agar and induce undifferentiated sarcomas in nude mice 10 .…”

Section: Introductionmentioning

confidence: 99%

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Phospholipases D1 and D2 regulate cell cycling in primary prostate cancer cells and are differentially associated with the nuclear matrix

Hogg

Bourgoin

et al. 2021

Preprint

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Phospholipases D1 and D2 (PLD1/2) have been implicated in tumorigenesis. We previously detected higher expression of PLD in the nuclei of patient-derived prostate cancer (PCa) cells and prostate cancer cell lines. Here we have examined whether PLD1 or PLD2 are associated with the nuclear matrix and influence cell cycling. PLD1/PLD2 were detected by qualitative immunofluorescence in cultured PCa cells and extracted with a standardised protocol to reveal nuclear matrix-associated proteins. The effects of isoform-specific inhibition of PLD1or PLD2 on PCa cell cycle progression were analysed by flow cytometry. PLD2 mainly co-localised with the nucleolar marker fibrillarin in PCa cells. However, even after complete extraction, some PLD2 remained associated with the nuclear matrix. Inhibiting PLD2 effectively reduced PCa cell cycling into and through S phase. In contrast, PLD1 inhibition effects were weaker, and a subpopulation of cycling patient-derived PCa cells was unaffected by PLD1 inhibition. When associated with the nuclear matrix PLD2 could generate phosphatidic acid to regulate nuclear mTOR and control downstream transcriptional events. The association of PLD2 with the nucleolus also implies a role in stress regulation. The cell cycling results highlight the importance of PLD2 inhibition as a novel potential prostate cancer therapeutic mechanism by differential regulation of cell proliferation.

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Section: Discussionmentioning

confidence: 83%

Section: Cell Isolation and Culturementioning

confidence: 99%

Section: Pld Inhibition and The Cell Cyclementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Phospholipases D1 and D2 regulate cell cycling in primary prostate cancer cells and are differentially associated with the nuclear matrix

Hogg

Bourgoin

et al. 2021

Preprint

Self Cite

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“…Thus, it is suggested that PLD1 might confer resistance to HDAC inhibitors. It has been reported that inhibition of PLD2 has therapeutic potential against cancers [ 31 – 34 ]. Herein, we show that PLD2 is upregulated by HDAC inhibitors in a transcriptional level.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of phospholipase D2 augments histone deacetylase inhibitor-induced cell death in breast cancer cells

Hwang¹,

Kang²,

Kang³

et al. 2020

Biol Res

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Background Histone deacetylase (HDAC) inhibitors are promising anticancer drugs but their effect on tumor treatment has been disappointing mainly due to the acquisition of HDAC inhibitor resistance. However, the mechanisms underlying such resistance remain unclear. Methods In this study, we performed Western blot, q-PCR, and promoter assay to examine the expression of HDAC inhibitor-induced phospholipase D2 (PLD2) in MDA-MB231and MDA-MB435 breast cancer cells. Apoptosis and proliferation were analyzed by flow cytometry. In addition to invasion and migration assay, angiogenesis was further measured using in vitro tube formation and chick embryo chorioallantoic membrane model. Results HDAC inhibitors including suberoylanilide hydroxamic acid (SAHA), trichostatin, and apicidin, induce expression of PLD2 in a transcriptional level. SAHA upregulates expression of PLD2 via protein kinase C-ζ in breast cancer cells and increases the enzymatic activity of PLD. The combination treatment of SAHA with PLD2 inhibitor significantly enhances cell death in breast cancer cells. Phosphatidic acid, a product of PLD activity, prevented apoptosis promoted by cotreatment with SAHA and PLD2 inhibitor, suggesting that SAHA-induced PLD2 expression and subsequent activation of PLD2 might confers resistance of breast cancer cells to HDAC inhibitor. The combinational treatment of the drugs significantly suppressed invasion, migration, and angiogenesis, compared with that of either treatment. Conclusion These findings provide further insight into elucidating the advantages of combination therapy with HDAC and PLD2 inhibitors over single-agent strategies for the treatment of cancer.

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Bone marrow mesenchymal stem cells promote prostate cancer cell stemness via cell–cell contact to activate the Jagged1/Notch1 pathway

Cheng

Duan

et al. 2021

Cell Biosci

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Background Mesenchymal stem cells (MSCs) play a crucial role in cancer development and tumor resistance to therapy in prostate cancer, but the influence of MSCs on the stemness potential of PCa cells by cell–cell contact remains unclear. In this study, we investigated the effect of direct contact of PCa cells with MSCs on the stemness of PCa and its mechanisms. Methods First, the flow cytometry, colony formation, and sphere formation were performed to determine the stemness of PCaMSCs, and the expression of stemness-related molecules (Sox2, Oct4, and Nanog) was investigated by western blot analysis. Then, we used western blot and qPCR to determine the activity levels of two candidate pathways and their downstream stemness-associated pathway. Finally, we verified the role of the significantly changed pathway by assessing the key factors in this pathway via in vitro and in vivo experiments. Results We established that MSCs promoted the stemness of PCa cells by cell–cell contact. We here established that the enhanced stemness of PCaMSCs was independent of the CCL5/CCR5 pathway. We also found that PCaMSCs up-regulated the expression of Notch signaling-related genes, and inhibition of Jagged1-Notch1 signaling in PCaMSCs cells significantly inhibited MSCs-induced stemness and tumorigenesis in vitro and in vivo. Conclusions Our results reveal a novel interaction between MSCs and PCa cells in promoting tumorigenesis through activation of the Jagged1/Notch1 pathway, providing a new therapeutic target for the treatment of PCa.

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Phospholipase D2 in prostate cancer: protein expression changes with Gleason score

Cited by 5 publications

References 111 publications

Phospholipases D1 and D2 regulate cell cycling in primary prostate cancer cells and are differentially associated with the nuclear matrix

Phospholipases D1 and D2 regulate cell cycling in primary prostate cancer cells and are differentially associated with the nuclear matrix

Inhibition of phospholipase D2 augments histone deacetylase inhibitor-induced cell death in breast cancer cells

Bone marrow mesenchymal stem cells promote prostate cancer cell stemness via cell–cell contact to activate the Jagged1/Notch1 pathway

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